Monocyte chemoattractant protein-1 (MCP-1) expression is found in malignant melanoma and melanoma metastases. Since areas of hypoxia/reoxygenation (H/R) are a common feature of malignant tumours and metastases, we addressed the question whether melanoma cells produce MCP-1 upon exposure to H/R. In the present study, we show that melanoma cells up-regulate MCP-1 mRNA and protein under H/R. By means of reporter gene analysis, we further demonstrate that H/R induces transcriptional activation of the MCP-1 promoter carrying a stimulatory protein-1 (SP1) and two nuclear factor-kappaB (NF-kappaB) binding motifs. Accordingly, H/R-stimulated melanoma cells showed enhanced binding activity of both transcription factors NF-kappaB and SP1 in electrophoretic mobility-shift assay. A common upstream activator of NF-kappaB, inhibitory kappaBalpha kinase, was not significantly activated under H/R conditions. Further analysis of upstream signalling events revealed that members of the mitogen-activated protein kinases family, namely extracellular signal-regulated protein kinase, c-Jun N-terminal kinase/ stress-activated protein kinase and p38 stress kinase, may be involved in MCP-1 transcriptional regulation under H/R. In summary, we conclude that H/R induces MCP-1 production in melanoma cells via the co-operative action of both transcription factors NF-kappaB and SP1, and involves mitogen-activated protein kinase signalling pathways. Functionally, H/R-induced MCP-1 production may contribute to tumour progression by committing selective pressure on tumour cells via chemoattraction and activation of tumour-infiltrating monocytes/macrophages.

Zoster is a frequent disease of adulthood with a distinct age-dependent increase after 60. In contrast during childhood or adolescence zoster only rarely occurs. Certain risk factors such as hematologic malignancies are associated with early appearance. The typical clinical manifestation is unilateral, equally involving thoracic dermatomes. A 16-year-old patient presented with zoster in bilateral asymmetrical distribution, with trigeminal and thoracic dermatomes simultaneously affected. Despite the clinical findings and the unusual localization, there was no history, clinical nor laboratory signs of an immune suppression or any other underlying disease. Careful follow-up examinations are necessary in order to recognize systemic, especially hematologic, malignancies.